engleski

Associations of cytokine gene polymorphisms with atopic diseases

We investigated associations of TNFα -308G>A, TNFα -238G>A, IL1α -889C>T and IL10 -1082G>A genetic polymorphisms with the atopic diseases (atopic rhinitis, atopic asthma and atopic dermatitis) with the adjustment for important lifestyle and environmental factors. Participants (N=356) were part of a larger study of atopic diseases in Croatian young adult population (median age 19 years ; range 18-29). Diagnosis of atopic asthma (AA), atopic rhinitis (AR) and atopic dermatitis (AD) was based on symptoms reported by modified “International Study of Asthma and Allergies in Childhood” questionnaire and positive skin prick test (SPT) to at least one common inhalatory allergen. Atopic respiratory disease was defined as having either or both atopic rhinitis and atopic asthma. Genetic polymorphisms TNFα -308G>A and -238G>A, IL1α -889C>T and IL10 -1082G>A were genotyped using polymerase chain reaction-based technique. After testing associations of polymorphism with atopic diseases in univariate analysis we performed multivariate analysis controlled for personal characteristics (gender, body mass index categories), lifestyle factors (cigarette smoking, pet ownership), environmental factors (urban/rural residency, residency in continental/Mediterranean region), and history of atopic disease in parents. There were 26 (7%) subject with AA, 63 (18%) with AR and 37 (10%) with AD. Among subjects with AA, 1 (4%) was TNFα -308G>A carrier, which was significantly lower than 76 (24%) carriers in non- AA subjects (Fisher’s exact = 0.022), but this association was not confirmed in multivariate analysis. Among subjects with AA and/or AR, i.e. atopic respiratory disease, 23 (35%) were IL1α -889C>T carriers, significantly less than 133 (50%) carriers among subject without atopic respiratory disease (Pearson chi2 = 4.647, p=0.031), and this result was confirmed in multivariate model for atopic respiratory disease (P model =0.000, pseudo R2 =0.26, OR=0.38, 95% CI 0.19-0.78, p =0.008) and AR alone (P model =0.000, pseudo R2 =0.38, OR=0.35, 95% CI 0.17-0.86, p =0.020). Finally, among subjects with AD, 3 (8%) were TNFα -308G>A carriers, which was significantly lower than 74 (25%) carriers in non- AD subjects (Fisher’s exact = 0.022), and this result was confirmed in multivariate model (P model =0.000, pseudo R2 =0.29, OR=0.21, 95% CI 0.05-0.91, p =0.038). There were no other significant associations of atopic diseases with studied polymorphisms. Overall, the most consistent results indicate the protective role of IL1α -889C>T genetic polymorphism regarding AR, and the protective role of TNFα -308G>A polymorphism regarding AD.

cytokine; polymorphism; asthma; rhinitis; dermatitis; atopy

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